Introduction: To achieve success in treatment, one cannot ignore the knowledge of pulp anatomy. Mandibular premolars are considered to be the most difficult teeth for endodontic therapy due to high variability in their canal morphology. It is possible that a relation exists between the crown size and the number of extra canals in these teeth, so this in vitro study aims to investigate the relationship between the crown size and the uncommon morphology of mandibular premolars using Cone-Beam Computed Tomography (CBCT). Materials and Methods: Eighty three extracted mandibular human premolars were exposed to radiation using the CBCT device. Root canal configuration was categorized according to the Vertucci’s classification. The crown size was measured in three axial, coronal and sagittal sections. Finally, the relation between these two factors was evaluated with variance analysis (two-way ANOVA) and chi-square. Results:: The most common canal type in the mandibular first and second premolars are type I (71% and 76%, respectively), followed by type V (29% and 22%, respectively). No significant relationship was found between the crown size and extra canals in mandibular premolars (P>0.05). Conclusion:: In this in vitro study, the average crown size in two-canalled second premolars was less than that in first premolars with a single canal; although the difference was not statistically significant. The research hypothesis was therefore rejected in both first and second mandibular premolars.